Amino acid compounds have generally been manufactured in the past by many different methods such as fermentation, hydrolysis, and organic synthesis. Alanine, for instance, has been synthesized by microbial fermentation or by utilizing a hydrolyzate thereof, and has also been produced by organic synthesis processes in which organic reagents are used.
The following are typical examples of conventional alanine synthesis.
a) Alanine synthesis by electrical oxidation of 3-amino-1-propanol in sulfuric acid using palladium electrodes
Reference 1: Jubilee Vol. Emil Barell, 1946, 85-91
b) Alanine synthesis from ethylenecyanohydrin
Reference 2: Boatright, U.S. Pat. No. 2,734,081 (1956 to Am. Cyanamid)
c) Alanine synthesis from methylaldehyde
Reference 3: E. C. Kendall & B. F. McKenzie, Org. Synth., 1, 21 (1941)
Reference 4: R. Draudry, Can. J. Res., 26B, 773 (1948)
d) β-Alanine synthesis from β-propiolactone
Reference 5: Ford, Org. Sys. Coll. Vol. 3, 34 (1955)
These and other methods that involve the use of electrode synthesis with a catalyst or ordinary synthesis have been employed.
Of the above methods, the Strecker method used in the synthesis of Reference 3, for example, has a long history as a method for synthesizing α-amino acids, but its great versatility still makes it useful. With this method, an aldehyde is reacted first with ammonia and then with hydrogen cyanide, and the intermediate product thus obtained is hydrolyzed with an acid or alkali to synthesize an α-amino acid with one extra carbon. In Reference 4, which makes use of the Bucherer method (which is an improved version of the above), alanine is synthesized using an alkali cyanide and ammonium carbonate. Since these two synthesis methods generate highly toxic hydrogen cyanide, they are considered to require the utmost caution (Shin Jikken Kagaku Koza [New Experimental Chemistry Lectures] 14, Synthesis and Reaction of Organic Compounds, Part 3, pp. 1673-1675, Maruzen (1978)]. Also, β-alanine has been synthesized by reacting β-propiolactone with ammonia in an acetonitrile solvent (Reference 5).
Thus, numerous factors have to be taken into account with conventional chemical synthesis methods, such as the disposal of organic solvents and toxic substrate substances used in the synthesis reaction, disposal of used catalysts, the danger to humans posed by by-products, and the safe usage of these substances. Also, the larger is the scale of this synthesis, the more serious these considerations become. Therefore, there is a need for the development of technology for disposing of used toxic substrate substances, organic solvents, catalysts, and so forth. Accordingly, the basic problems outlined above could be solved if some completely new synthesis method that did not involve the use of these toxic substrate substances, organic solvents, catalysts, and so forth could be developed.
In light of this situation, and in view of the prior art discussed above, the inventors conducted research into a method for introducing an amino group into an organic acid or an organic ester under high temperature and pressure, whereupon they discovered that an amino group can be introduced into an organic acid or organic ester by reacting an organic salt or an organic ester and ammonia or an ammonium salt compound under high-temperature and high-pressure water conditions, and perfected the present invention upon conducting follow-up research based on this finding.
The present invention provides a method for introducing an amino group, a method for synthesizing an amino acid compound, and a method for manufacturing an amino acid compound, all under high-temperature and high-pressure water conditions.
The present invention is a method for introducing an amino group, wherein an amino group is introduced into an organic acid or an organic ester by reacting an organic salt or an organic ester with ammonia under high-temperature and high-pressure water conditions; a method for synthesizing an amino acid compound, wherein an organic salt or an organic ester is reacted with ammonia under high-temperature and high-pressure water conditions, and an amino group is introduced into the organic acid or the organic ester, thereby synthesizing an amino acid or an amino ester; and a method for manufacturing an amino acid compound, wherein an organic salt or an organic ester is reacted with ammonia under high-temperature and high-pressure water conditions, an amino group is introduced into the organic acid or organic ester to synthesize an amino acid or an amino ester, and this product is then separated and refined with an ion exchange resin.